Genome complexity: epigenetics in cell division (Introduction)

by David Turell @, Friday, May 08, 2015, 15:01 (1510 days ago) @ David Turell

A complex article about a protein that helps control cell division and can modify gene expression:

"A new study by researchers at the Perelman School of Medicine at the University of Pennsylvania published in Science this week describes how the centromere is stabilized during replication. DNA in the nucleus is packaged into protein/DNA complexes called nucleosomes. As it turns out, the centromere is distinguished not only by its DNA sequence but also by a special type of nucleosome, which includes a protein called CENP-A.

"Their findings also address the question of the stability of CENP-A molecules at centromeres. Under normal conditions CENP-A binds centromeres and effectively never lets go. Indeed, when the authors tracked where proteins "reside" in live cells, they found that, unlike traditional nucleosomes that package the DNA throughout the rest of the chromosome, CENP-A-containing nucleosomes apparently never dissociate after newly generated CENP-A protein is first delivered to the centromere during a short time window following cell division. "The CENP-A is basically cemented at the centromere of origin," Black explains. But in cells lacking CENP-C, CENP-A dissociates readily, suggesting that CENP-C binding to CENP-A is what imparts that stability.

"Investigators have known for the past 20 years that part of chromosome inheritance is controlled by epigenetics, implicating the protein spools around which DNA is wound as the driving force, rather than what is encoded in the DNA sequence itself. Those spools are built of histone proteins, and chemical changes to these spool proteins can either loosen or tighten their interaction with DNA. This, in turn, alters a gene's expression up or down. In the case of the centromere, it marks the site where spindle fibers attach independently of the underlying DNA sequence.

"Black notes that these data suggest a model of epigenetic biology distinct from the traditional view of nucleosomes as static scaffolds on which key functional molecules assemble. Instead, the team's data suggest that histone variants and post-translational modifications, which change the biological properties of nucleosomes through changes in shape (by adding or removing enzyme docking sites) make nucleosomes active participants in cell division and gene expression.

"This mode of nucleosome regulation and stabilization may well be common to other epigenetic processes, Black adds. Indeed, he says the results suggest that other histone variants and histone post-translational modifications may serve a similar function as the example at the centromere with CENP-A and CENP-C, for instance in the regulation of gene expression.

"'I don't know how widely this occurs," he says, "but I'd be very surprised if this was the only place in nature that had evolved to take advantage of the fact that the shape of nucleosomes can be regulated by protein-binding events.'"

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